English A, Jones E A, Corscadden D, Henshaw K, Chapman T, Emery P, McGonagle D
The Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK.
Rheumatology (Oxford). 2007 Nov;46(11):1676-83. doi: 10.1093/rheumatology/kem217. Epub 2007 Sep 26.
The utility of autologous chondrocytes for cartilage repair strategies in older subjects with osteoarthritis (OA) may be limited by both age-related and disease-associated decline in chondrogenesis. The aim of this work was to assess OA Hoffa's fat pad as an alternative source of autologous chondroprogenitor cells and to compare it with OA chondrocytes derived from different areas of cartilage.
Cartilage and fat pad tissue digests were obtained from 26 subjects with knee OA and compared with normal bone marrow (BM) mesenchymal stem cells (MSCs) with respect to their in vitro colony-forming potential, growth kinetics, multipotentiality and clonogenicity. Flow cytometry was used to investigate their MSC marker phenotype.
Expanded cultures derived from eroded areas of cartilage were slightly more chondrogenic than those derived from macroscopically normal cartilage or chondro-osteophytes; however, all cartilage-derived cultures failed to maintain their chondrogenic potency following extended expansion. In contrast, OA fat pads contained highly clonogenic and multipotential cells with stable chondrogenic potency in vitro, even after 16 population doublings. Standard colony-forming assays failed to reflect the observed functional differences between the studied tissues whereas flow cytometry revealed higher levels of a putative MSC marker low-affinity growth factor receptor (LNGFR) on culture expanded fat pad-derived, but not cartilage-derived, MSCs.
In contrast to OA cartilage from three different sites, OA Hoffa's fat pad contains clonogenic cells that meet the criteria for MSCs and produce multipotential cultures that maintain their chondrogenesis long term. These findings have broad implications for future strategies aimed at cartilage repair in OA.
在患有骨关节炎(OA)的老年受试者中,自体软骨细胞用于软骨修复策略的效用可能受到与年龄相关的软骨生成下降以及疾病相关因素的限制。本研究旨在评估OA Hoffa脂肪垫作为自体软骨祖细胞的替代来源,并将其与源自软骨不同区域的OA软骨细胞进行比较。
从26例膝OA患者获取软骨和脂肪垫组织消化物,并与正常骨髓(BM)间充质干细胞(MSC)在体外集落形成潜力、生长动力学、多能性和克隆形成能力方面进行比较。采用流式细胞术研究其MSC标志物表型。
源自软骨侵蚀区域的扩增培养物的软骨生成能力略高于源自宏观正常软骨或软骨骨赘的培养物;然而,所有源自软骨的培养物在长期扩增后均未能维持其软骨生成能力。相比之下,OA脂肪垫含有高度克隆形成和多能的细胞,即使在传代16次后,在体外仍具有稳定的软骨生成能力。标准集落形成试验未能反映所研究组织之间观察到的功能差异,而流式细胞术显示,培养扩增的源自脂肪垫而非软骨的MSC上,一种假定的MSC标志物低亲和力生长因子受体(LNGFR)水平更高。
与来自三个不同部位的OA软骨不同,OA Hoffa脂肪垫含有符合MSC标准的克隆形成细胞,并能产生长期维持软骨生成能力的多能培养物。这些发现对未来旨在OA软骨修复的策略具有广泛的意义。